Download PDF

Explore for Yourself

RNA Interference

Advancements in Drug Discovery and Recently Achieved Milestones

Select References

General reviews

Biology's Big Bang: Unravelling the secrets of RNA. Cover, The Economist, June 16, 2007 edition.

Dykxhoorn, D.M. & Lieberman, J. (2006). Knocking down disease with siRNAs. Cell 126: 231-5.

de Fougerolles, A., Vornlocher, H.P., Maraganore, J. & Lieberman, J. (2007). Interfering with disease: a progress report on siRNA-based therapeutics. Nat. Rev. Drug Discov. 6: 443-53.

Kim, D.H. & Rossi, J.J. (2007). Strategies for silencing human disease using RNA interference. Nat. Rev. Genet. 8: 173-84.

Kim, V.N. (2005). MicroRNA biogenesis: coordinated cropping and dicing. Nat. Rev. Mol. Cell. Biol. 6: 376-85.

Meister, G. & Tuschl, T. (2004). Mechanisms of gene silencing by double-stranded RNA. Nature 16: 343-9.

Add Dirk's article on the "business of RNAi"

Key scientific milestones (in chronological order)

RNAi

Napoli, C., Lemieux, C. & Jorgensen, R. (1990). Introduction of a chimeric chalcone synthase gene into petunia results in reversible co-suppression of homologous genes in trans. Plant Cell 2: 279-89.
Co-suppression phenomenon in plants. Later shown to be caused by RNAi.

Fire, A., Xu, S., Montgomery, M.K., Kostas, S.A., Driver, S.E. & Mello, C.C. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391: 806-11.
Breakthrough discovery that long double-stranded RNAs trigger RNAi in lower organisms.

Hamilton, A.J. & Baulcombe, D.C. (1999). A species of small antisense RNA in post-transcriptional gene silencing in plants. Science 286: 950-2.
Small RNAs observed during RNAi in plants.

Zamore, P.D., Tuschl, T., Sharp, P.A. & Bartel, D.P. (2000). RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 101: 25-33.

Elbashir, S.M., Lendeckel, W. & Tuschl, T. (2001). RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev. 15: 188-200.
Pair of distinct papers demonstrating that long double-stranded RNAs are processed into small RNAs in fly cell extract and that these guide mRNA cleavage during RNAi.

Elbashir, S.M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K. & Tuschl, T. (2001). Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411: 494-8.
Small double-stranded small RNAs with 2 nucleotide 3' overhangs, siRNAs, trigger efficient RNAi gene silencing in cultured mammalian cells.

McCaffrey, A.P., Meuse, L., Pham, T.T., Conklin, D.S., Hannon, G.J. & Kay, M.A. (2002). RNA interference in adult mice. Nature 418: 38-39.
RNAi in an adult mammalian organism.

Soutschek, J. et al. (2004). Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432: 173-8.
RNAi in mice following the systemic administration of siRNAs.

Zimmermann, T.S. et al. (2006). RNAi-mediated gene silencing in non-human primates. Nature 441: 111-4.
RNAi in a non-human primate following the systemic administration of siRNAs.

MicroRNA

Lee, R.C., Feinbaum, R.L. & Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75: 843-54.
Discovery of the first miRNA..

Lagos-Quintana, M., Rauhut, R., Lendeckel, W. & Tuschl, T. (2001). Identification of novel genes coding for small expressed RNAs. Science 26: 797-9. MiRNAs represent an abundant class of small RNAs found in most organisms, including humans.

Kruetzfeld, J., Rajewski, N., Braich, R., Rajeev, K.G., Tuschl, T., Manoharan, M. & Stoffel, M. (2005). Silencing of microRNAs in vivo with 'antagomirs'. Nature 438: 685-9. Functional miRNA inhibition by antisense technology in an adult mammal.

Additional Resources

Introduction to RNAi by PBS Nova:
http://www.pbs.org/wgbh/nova/sciencenow/3210/02.html

Wikipedia online encyclopedia entry on RNAi:
http://en.wikipedia.org/wiki/RNA_interference

Animation of RNAi by Nature:
http://www.nature.com/focus/rnai/animations/index.html

Press release by the Nobel Assembly on the 2006 Nobel Prize in Physiology or Medicine to Andrew Z. Fire and Craig C. Mello for their discovery of RNAi:
http://nobelprize.org/nobel_prizes/medicine/laureates/2006/press.html

Science magazine 2002 Breakthrough of the Year special issue:
http://www.sciencemag.org/content/vol298/issue5602/#special

RNAi.net portal on RNAi:
http://www.rnai.net/